Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

This study was designed to comprehensively characterize and identify the chemical components in traditional Chinese medicine Psoraleae Fructus by establishing an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) method in combination with in-house library. The chromatographic separation conditions(stationary phase, column temperature, mobile phase, and elution gradient) and key MS monitoring parameters(capillary voltage, nozzle voltage, and fragmentor) were sequentially optimized via single-factor experiments. A BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was finally adopted, with the mobile phase consisting of 0.1% formic acid in water(A) and acetonitrile(B) at the flow rate of 0.4 mL·min~(-1) and column temperature of 30 ℃. Auto MS/MS was utilized for data acquisition in both positive and negative ion modes. By comparison with reference compounds, analysis of the MS~2 fragments, in-house library retrieval and literature research, 83 compounds were identified or tentatively characterized from Psoraleae Fructus, including 58 flavonoids, 11 coumarins, 4 terpenoid phenols, and 10 others. Sixteen of them were identified by comparison with reference compounds, and ten compounds may have not been reported from Psoraleae Fructus. This study achieved a rapid qualitative analysis on the chemical components in Psoraleae Fructus, which provided useful reference for elucidating its material basis and promoting the quality control.
Chromatography, High Pressure Liquid ; Medicine, Chinese Traditional ; Tandem Mass Spectrometry ; Cell Cycle ; Coumarins

Objective: To provide a new solution for the digital design of nasal prostheses, this study explores the three-dimensional (3D) facial morphology completion method for external nasal defects based on the non-rigid registration process of 3D face template. Methods: A total of 20 male patients with tooth defect and dentition defect who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to December 2022 were selected, age 18-45 years old. The original 3D facial data of patients were collected, and the 3D facial data of the external nose defect was constructed in Geomagic Wrap 2021 software. Using the structured 3D face template data constructed in the previous research of the research group, the 3D face template was deformed and registered to the 3D facial data of external nose defect (based on the morphology of non-defective area) by non-rigid registration algorithm (MeshMonk program), and the personalized deformed data of the 3D face template was obtained, as the complemented facial 3D data. Based on the defect boundary of the 3D facial data of the external nose defect, the complemented external nose 3D data can be cut out from the complemented facial 3D data. Then the nasofacial angle and nasolabial angle of the complemented facial 3D data and the original 3D facial data was compared and analyzed, the ratio between the nose length and mid-face height, nose width and medial canthal distance of the complemented facial 3D data was measured, the edge fit between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was evaluated, and the morphological difference of the nose between the complemented external nose 3D data and the original 3D facial data was analyzed. Results: There was no significant statistically difference (t=-0.23, P=0.823; Z=-1.72, P=0.086) in the nasofacial angle (28.2°±2.9°, 28.4°±3.5° respectively) and nasolabial angle [95.4°(19.2°), 99.9°(9.5°) respectively] between the 20 original 3D facial data and the complemented facial 3D data. The value of the ratio of nose length to mid-face height in the complemented facial 3D data was 0.63±0.03, and the value of the ratio of nose width to medial canthal distance was 1.07±0.08. The curve deviation (root mean square value) between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was (0.37±0.09) mm, the maximum deviation was (1.14±0.32) mm, and the proportion of the curve deviation value within±1 mm was (97±3)%. The distance of corresponding nose landmarks between the complemented facial 3D data and the original 3D facial data were respectively, Nasion: [1.52(1.92)] mm; Pronasale: (3.27±1.21) mm; Subnasale: (1.99±1.09) mm; Right Alare: (2.64±1.34) mm; Left Alare: (2.42± 1.38) mm. Conclusions: The method of 3D facial morphology completion of external nose defect proposed in this study has good feasibility. The constructed complemented external nose 3D data has good facial coordination and edge fit, and the morphology is close to the nose morphology of the original 3D facial data.

Osteoarthritis (OA) is a common degenerative disease of the motor system with a high morbidity and disability rate. The pathogenesis of OA is not clear at present. Previous studies believe that the pathogenesis of OA is mainly related to trauma factors, while recent studies have shown that metabolic factors, including abnormal cholesterol metabolism, are also closely related to OA. The treatment of OA is mainly symptomatic treatment at the early stage and surgical treatment at the late stage, and there is no specific drug. Previously, BNTA, a small molecule drug with cartilage protective effects, has been shown to have a good effect on OA caused by trauma, but its effect on OA caused by high cholesterol remains unclear. In order to explore the therapeutic effect of BNTA on OA caused by high cholesterol and its mechanism, the OA model of rats was constructed by adopting high cholesterol diets, and paraffin sections of knee joints were taken for histological evaluation. Lipid accumulation in chondrocytes of rats was assessed by oil red O staining. The expression of genes and proteins related to anabolism, catabolism and cholesterol metabolism in chondrocytes was assessed by RT-qPCR, immunofluorescence and immunohistochemistry. The results showed that BNTA could alleviate OA pathological manifestations and improve the OARSI (Osteoarthritis Research Society International) score in the OA model of high cholesterol rats. In rat chondrocytes, BNTA can promote the expression of anabolism-related genes col2, sox9 and acan, inhibit the expression of catabolism-related genes mmp13 and adamts5, and improve the lipid accumulation caused by high cholesterol in rat chondrocytes. BNTA can up-regulate Insig1 expression in rat chondrocytes and the OA model of high cholesterol rats. This study confirmed that high cholesterol can aggravate OA in vivo and in vitro, and can increase lipid accumulation in rat chondrocytes. Taken together, BNTA can alleviate OA phenotypes induced by high cholesterol and improve abnormal lipid accumulation in chondrocytes, possibly by inhibiting cholesterol biosynthesis in cells by upregulating Insig1, thereby alleviating abnormal lipid accumulation.

The pharmacological effects of Angelicae Sinensis Radix from different producing areas are uneven. Accurate identification of its producing areas by computer vision and machine learning(CVML) is conducive to evaluating the quality of Angelicae Sinensis Radix. This paper collected the high-definition images of Angelicae Sinensis Radix from different producing areas using a digital camera to construct an image database, followed by the extraction of texture features based on the grayscale relationship of adjacent pixels in the image. Then a support vector machine(SVM)-based prediction model for predicting the producing areas of Angelicae Sinensis Radix was built. The experimental results showed that the prediction accuracy reached up to 98.49% under the conditions of the model training set occupying 80%, the test set occupying 20%, and the sampling radius(r) of adjacent pixels being 2. When the training set was set to 10%, the prediction accuracy was still over 93%. Among the three producing areas of Angelicae Sinensis Radix, Huzhu county, Qinghai province exhibited the highest error rate, while Heqing county, Yunnan province the lowest error rate. Angelicae Sinensis Radix from Minxian county, Gansu province and Huzhu county, Qinghai province were both wrongly attributed to Heqing county, Yunnan province, while most of those from Huzhu county, Qinghai province were misjudged as the samples produced in Minxian county, Gansu province. The method designed in this paper enabled the rapid and non-destructive prediction of the producing areas of Angelicae Sinensis Radix, boasting high accuracy and strong stability. There were definite morphological differences between Angelicae Sinensis Radix samples from Minxian county, Gansu province and those from Huzhu county, Qinghai province. The wrongly predicted samples from Minxian county, Gansu province and Huzhu city, Qinghai province shared similar morphological characteristics with those from Heqing county, Yunnan province. Most wrongly predicted samples from Heqing county, Yunnan province were similar to the ones from Minxian county, Gansu province in morphological characteristics.
Angelica sinensis ; China ; Databases, Factual ; Drugs, Chinese Herbal/analysis* ; Plant Roots/chemistry*

Objective: To investigate the effect of casein kinase 2 interacting protein-1 (CKIP-1) on craniofacial soft tissues and hard tissues, to provide the basis for the study and treatment of craniomaxillofacial related diseases. Methods: 6-month- old male CKIP-1 knockout (KO) mice were selected as the experimental group, and wild-type (WT) mice were selected as the control group. The craniomaxillofacial hard tissues (parietal bone, nasal bone, incisors and molars) were analyzed through micro- CT, and the morphological changes of maxillofacial soft tissues (nasal cartilage, lip mucosa and tongue) were analyzed through HE staining and toluidine blue staining. Results: CKIP-1 negatively regulated bone mass of cancellous bone of cranial and maxillofacial bones and dentin mineralization. Compared with the WT mice, the thickness of the parietal baffle layer increased by 93% in KO mice, while cortical bone showed no significant difference between the two groups. The nasal cancellous bone thickness increased by 160% in KO-mice, while cortical bone showed no significant difference between the two groups; the enamel thickness was normal, but the pulp cavity became smaller and the dentin thickness increased by 48%. Compared with the WT mice, the HE staining and toluidine blue staining analyses of the soft tissues revealed that the thickness of the alar cartilage plate of KO mice increased by 57%, and local ossification was found within the cartilage plate. The thickness of the keratinized layer of the labial mucosa increased by 170% in KO mice and the muscle fiber diameter of the lingual muscle increased by 45%. Conclusion CKIP-1 genes have different effects on the growth and development of various soft and hard tissues in the maxillofacial region of mice.

Objective: To understand and compare the differences in help-seeking behavior among junior high school students and senior high school students and their association with non-suicidal self-injury to provide a basis for the prevention and control of non-suicidal self-injury among middle school students. Methods: Three middle schools in Nanchang were selected,and the survey were conducted among 4 434 students through the General Situation Questionnaire, the Ottawa Self-injury Judgment Entry, and the Middle School Students Help Seeking Behavior Questionnaire, and SPSS 22.0 was used for statistical analysis. Results: The NSSI detection rate among middle school students was 33.3% , and junior high school students detection rate(36.0%) were higher than high school students(29.6%) (χ 2=19.41，P<0.01). Differences in willingness to ask for help, asking for help from family and teachers, and talking face-to-face for help were statistically significant (all P<0.01) among NSSI participants and non-NSSI participants, for both junior high school and high school students. Females (OR=1.45), class cadres (OR=1.26), urban household registration (OR=1.45), frequent scolding by elders (OR=1.98) and a high academic burden (OR=1.39) all possible increased the risk of NSSI in junior high school students, while assistance to family members (OR=0.95) or teachers (OR=0.95) possible reduced the risk of NSSI in junior high school students. Females (OR=1.50), class cadres (OR=1.34), only children (OR=1.45), fathers with college education and above (compared to junior high school and below) (OR=1.56), frequent scolding by elders (OR=2.08), frequent corporal punishment from elders (OR=4.12) and high academic burden (OR=1.38) possibly increased the risk of NSSI among high school students, while willingness to ask for help (OR=0.82), asking for help from family (OR=0.95) and teachers (OR=0.96) possible reduced the risk of NSSI among high school students. Conclusion There are some differences in help-seeking behavior between junior and high school students, and school and parents should actively focus on middle school students help-seeking behavior and encourage them to seek help.

Management of bone defects caused by fractures，bone tumors or infections is clinically difficult as well as a hot topic in current studies. With further researches over bone defects，the construction of tissue-engineered bone has played a great role in the treatment of bone defects. Blood vessels not only provide the necessary nutritional mineral salts，growth factors，hormones for bone formation，also are able to mediate the interaction among osteoblasts and osteoclasts，osteocytes，bone autonomic nerve and endothelial cells，since bone formation exist spatially and temporally connection with angiogenesis. Therefore，the authors make a systematic literature review on the research progress of the coupling mechanism of angiogenesis and osteogenic differentiation，blood vessels and related signal pathways on osteogenic differentiation and angiogenesis-related molecules in osteogenic differentiation during the process of traumatic bone defects，so as to provide new ideas for the treatment of bone defects.

Objective To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) of Monaco planning system for nasopharyngeal carcinoma between Pareto and Constrained optimization in order to provide a reference for future mode selection. Methods Select 20 patients with nasopharyngeal carcinoma whom were calculated by Pareto and Constrained modes in the same CT image. Prescription dose of target PGTV, PTV1 and PTV2 was 70.29、60.39 and 54.45 Gy with 33 fractions, 5 times a week. The differences in target dose, organs at-risk dose, monitor units and segments were compared in the condition of 95% of the target volume reached the prescribed dose. Results Compared with Pareto group, Constrained group achieved a better HI and CI. CI of PGTV and PTV1 signed statistical differences (P < 0.05). Dose of OARs in Constrained group were all lower than those in Pareto group except Optical-l and lens-l. The differences of spinal cord prv dose and V₃₀ of Parotid-r between two groups was significant (P < 0.05) while the differences of monitor units and segments between two groups was not significant (P > 0.05). Conclusion The length of middle turbinate is negatively correlated with the occurrence and severity of CMS. There is no significant correlation between the degree of curling and the occurrence of CMS, but patients with lower degree of curling of middle turbinate may have more serious CMS.

Objective:To investigate the effects of severe famine exposure during early life on their later adult obesity/central obesity.Methods:We recruited 4 495 subjects who were born before and during 3 years of unpredictable natural disasters in China and from Guiyang subcenter of the Risk Evaluation of cAncers in Chinese diabeTic Individual: a lONgitudinal (REACTION) Study for data analysis. The subjects were divided into childhood exposure group(born from October 1, 1954 to September 30, 1956, n=947), infant exposure group(born from October 1, 1956 to September 30, 1958, n=939), fetal exposure group(born from October 1, 1959 to September 30, 1961, n=525), and control group(born from October 1, 1952 to September 30, 1954 and from October 1, 1962 to September 30, 1964, n=1 525) according to their birth date. Obesity was defined as body mass index (BMI)≥28 kg/m 2, and central obesity was defined as waist circumference≥90 cm in men and ≥85 cm in women. We used logistic regression models to assess the effect of severe famine exposure on adult obesity/central obesity. Results:After adjusting for confounding factors, we found that men in the fetal exposure group had higher risk of adult obesity than the control group( OR=2.817, 95% CI 1.120-7.088, P=0.028), women in the fetal exposure group( OR=2.383, 95% CI 1.517-3.743, P=0.000), and infant exposure group( OR=1.554, 95% CI 1.039-2.324, P=0.032) had higher risk of adult obesity than the control group. In addition, compared with the control group, the male fetal exposure group had an increased risk of adult central obesity ( OR=2.440, 95% CI 1.253-4.752, P=0.009), which was unfound in females. Conclusion:Severe famine exposure during earlylife, especially in fetus and female infancy, increases the risk of obesity in their adulthood. In addition, males who experienced severe famine in their fetuses period may have higher risks of central obesity when reaching adulthood.